In the last few years there has been a resurgence in non-injecting use of heroin. In New York City alone, tens of thousands of non-injecting users (NIUs) of heroin are at high risk of reverting to or initiating injecting drug use and of eventually becoming infected with the human immunodeficiency virus (HIV) and other blood-borne pathogens. They also are at risk of becoming infected by engaging in unsafe sex. Among those who go on to inject, some new injectors may be at particularly increased risk of infection with HIV during the early part of their injection careers. Since little is known about heroin NIUs, the proposed research will provide knowledge which can help to develop policies and programs to prevent transitions to drug injecting by heroin NIUs, to encourage those who start to inject to stop, and to prevent them from engaging in unsafe sex. The first and most important aim of the research is to determine, among heroin NIUs who are not current injectors, the rate at which they progress/revert to injecting drug use, and the predictors of such progression/reversion. Other aims are to determine: (2) the extent of and predictors of high-risk sexual behavior and high-risk sexual networks, and of changes in high-risk sexual behavior and high-risk sexual networks; (3) among those who become injectors, the extent to which they then engage in high-risk injecting behaviors and have high-risk drug networks, and the predictors of such behaviors and networks; (4) the extent and predictors of prevalent infection with HIV, hepatitis B (HBV) and hepatitis C (HCV) among those who have and have not previously injected drugs; and (5) the incidence rates of infection with HIV, HBV and HCV, and the predictors of HBV and HCV infection, among those who do and do not go on to inject. The study will be a prospective cohort study of 1,300 heroin NIUs in New York who will be recruited from multiple out-of-treatment settings. They will be interviewed and tested, and given three follow-up interviews at six month intervals. These data will be analyzed for predictors of transitions and incidence rates using nested case-control techniques and person-years methods such as Cox proportional hazards regression. Ethnographic data will be collected through field observation and intensive interviews, and will be analyzed using grounded theory techniques. Analytic emphasis will be placed on determining specific causes that induce or restrain NIUs from injecting (and among those who do begin/revert to injecting, factors that lead to particularly high-risk behaviors or to injecting drugs in particularly high-risk networks). Possible causes include: (1) specific kinds of social relationships, including both social support networks and risk networks; (2) specific kinds of social integration or marginalization; (3) personal susceptibility factors; and (4) drug market conditions such as purity, availability and cost. On the bases of these analyses, suggestions and proposals will be developed to prevent NIUs from progressing/reverting to injecting. Such programs could literally save tens of thousands of lives.